Influence of plasma glutathione levels on radiation mucositis

Purpose: To test the hypothesis that there is a link between plasma glutath ione (GSH) or other antioxidants (uric acid. ascorbate) and the severity of radiation mucositis following radiation treatment of tumors of the head an d neck. Patients and Methods: Patients with carcinomas of the head-and-neck region were treated with the continuous hyperfractionated accelerated radiotherapy (CHART) regimen (54 Gy in 36 fractions over 12 days). Samples of blood pla sma were analyzed for GSH, cysteine, urate, and ascorbate by high-pressure liquid chromatography. Patients were graded for dysphagia and requirement f or analgesics. The areas under the curves of scores over 2-6 weeks followin g treatment were computed, and Spearman's rank-correlation coefficient was used to test for an association between plasma GSH levels (or those of othe r antioxidants) and mucositis. Results: The pretreatment plasma GSH level in 18 patients scored in the stu dy was 1.0 +/- 0.7 muM. Analysis of these and the dysphagia scores produced a correlation coefficient of 0.22 (confidence interval -0.28, 0.61; p = 0. 39). No correlation was seen between mucositis severity and other measures of plasma antioxidants: cysteine (7.6 +/- 1.7 muM), cysteine + GSH (8.6 +/- 1.9 muM), uric acid (317 +/- 86 muM), ascorbate (29 +/- 20 muM), or whole- blood GSH concentrations (1,010 +/- 239 muM). Conclusion: The measurements of approximately micromolar levels of plasma G SH, or about 10 muM cysteine + GSH (almost all of the total nonprotein thio ls), are consistent with most other published data for either healthy adult s or cancer patients; however, the values reported in an earlier study, sug gesting a link between GSH and mucositis, are much higher. The hypothesis o f a possible link between radiation mucositis and plasma-free (nonprotein) thiols was not supported. (C) 2001 Elsevier Science Inc.